Fluorescence Spectroscopy is inherently a very sensitive technique; it already forms the basis of most non-radioactive real time assays like PCR. Our lab has collaborated with former fellows (now in biotech industry) to develop alternatives to PCR like CataCleave probes for SNPs, leading to publication. We also have studied the coupling of DNA components to multilayer metal nanoparticles for much faster PCR analysis and the use of FCS (see MPM report) to quantify very tight protein-protein and protein-DNA binding in sub-microliter drops (analytes are present in sub-femtomole amounts). We previously examined the structural transitions of similar amounts of DNA between G-quadruplexed and linear forms, using both MPM-FCS and Time-Resolved Fluorescence tools, with the goal of developing very sensitive 'G-quad' detection assays. We have combined time-resolved detection with translational mobility (FCS) to help identify free and bound signatures for assay. We are now preparing a RICS /FCCS microscope for combining the techniques mentioned above.